Gecacitinib Combined With Donafenib and PD-1 Inhibitor as Immune Rechallenge Therapy for Unresectable Hepatocellular Carcinoma

NCT ID: NCT07157306

Last Updated: 2025-09-05

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-10
• Study Completion Date: 2028-01-01

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of Gecacitinib Combined With Donafenib and PD-1 Inhibitor as Immune Rechallenge Therapy for Unresectable Hepatocellular Carcinoma

Detailed Description

Jak inhibitors have already demonstrated the ability to reverse T-cell exhaustion in the treatment of Hodgkin lymphoma. Gecacitinib is a Jak inhibitor that has been approved for the treatment of bone marrow fibrosis. This study was designed to evaluate the safety and efficacy of Gecacitinib Combined With Donafenib and PD-1 Inhibitor as Immune Rechallenge Therapy for Unresectable Hepatocellular Carcinoma . Total 35 subjects will be recruited in this study, ORR will be will be used as primary outcome measures, OS, PFS, DCR and safety will be the secondary endpoints.

Conditions

Hepatocellular Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

study arm

The participants in this arm will be treated with combination therapy of Gecacitinib（100mg,Bid,po）, Donafenib (200mg,Bid,po), and PD-1(Q3W,iv).

Group Type: EXPERIMENTAL

Gecacitinib Combined With Donafenib and PD-1 Inhibitor

Intervention Type: DRUG

Subjects were enrolled and started receiving treatment with Gecacitinib (100mg, Bid, po) for 7 consecutive days; thereafter, they were treated with PD-1 antibody (Q3W, iv) and Donafenib (200mg, Bid, po), counting the day of infusion of PD-1 monoclonal antibodies as C1D1, with each cycle lasting 3 weeks. Subsequent treatments involved administering Gecacitinib for 1 week before each infusion of PD-1.

Interventions

Gecacitinib Combined With Donafenib and PD-1 Inhibitor

Subjects were enrolled and started receiving treatment with Gecacitinib (100mg, Bid, po) for 7 consecutive days; thereafter, they were treated with PD-1 antibody (Q3W, iv) and Donafenib (200mg, Bid, po), counting the day of infusion of PD-1 monoclonal antibodies as C1D1, with each cycle lasting 3 weeks. Subsequent treatments involved administering Gecacitinib for 1 week before each infusion of PD-1.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age and gender: >18 years old and≤75 years old, both men and women.

2. All subjects must have Hepatocellular Carcinoma confirmed by pathological or clinical diagnosis.

3. Patients with viable and measurable target lesion per RECIST 1.1.

4. Patients with unresectable hepatocellular carcinoma (uHCC) who experienced disease progression after first-line therapy containing immune checkpoint inhibitors.

5. Patients who are expected to live more than 3 months.

9.ECOG PS 0-1. 10.Child-Pugh ≤7.

Exclusion Criteria

1. Fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma confirmed by histology or cytology.

2. History of malignant tumor, excluding the following cases:

1. Malignant tumor that was curatively treated more than 5 years prior to study entry and has not recurred since then;

2. Successful radical resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder carcinoma, preinvasive cervix carcinoma, and other preinvasive cancers.

3. Diffuse tumor lesion.

4. Preexisting or history of hepatic encephalopathy, hepatorenal syndrome or liver transplantation.

5. Clinically uncontrolled ascites or pleural effusion.

6. Received treatment with a JAK inhibitor previously .

7. Clinically severe gastrointestinal bleeding within 6 months of the start of treatment or any life-threatening bleeding events within 3 months of the start of treatment.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tianjin Medical University Cancer Institute and Hospital

OTHER

Sponsor Role: lead

Responsible Party

Wei Zhang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, China

Countries

China

Central Contacts

Wei Zhang

Role: CONTACT

zhang.wei@tmu.edu.cn

86-2223340123 Ext. 3090

References

Mathew D, Marmarelis ME, Foley C, Bauml JM, Ye D, Ghinnagow R, Ngiow SF, Klapholz M, Jun S, Zhang Z, Zorc R, Davis CW, Diehn M, Giles JR, Huang AC, Hwang WT, Zhang NR, Schoenfeld AJ, Carpenter EL, Langer CJ, Wherry EJ, Minn AJ. Combined JAK inhibition and PD-1 immunotherapy for non-small cell lung cancer patients. Science. 2024 Jun 21;384(6702):eadf1329. doi: 10.1126/science.adf1329. Epub 2024 Jun 21.

Reference Type: BACKGROUND

PMID: 38900877 (View on PubMed)

Zak J, Pratumchai I, Marro BS, Marquardt KL, Zavareh RB, Lairson LL, Oldstone MBA, Varner JA, Hegerova L, Cao Q, Farooq U, Kenkre VP, Bachanova V, Teijaro JR. JAK inhibition enhances checkpoint blockade immunotherapy in patients with Hodgkin lymphoma. Science. 2024 Jun 21;384(6702):eade8520. doi: 10.1126/science.ade8520. Epub 2024 Jun 21.

Reference Type: BACKGROUND

PMID: 38900864 (View on PubMed)

Other Identifiers

E20250854

Identifier Type: -

Identifier Source: org_study_id